Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Debackere, K.; Marcelis, L.; Demeyer, S.; Vanden Bempt, M.; Mentens, N.; Gielen, O.; Jacobs, K.; Broux, M.; Verhoef, G.; Michaux, L.; Graux, C.; Wlodarska, I.; Gaulard, P.; de Leval, L.; Tousseyn, T.; Cools, J.; Dierickx, D.

doi:10.1038/s41467-021-24037-4

Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Details

Download: 41467_2021_Article_24037.pdf (5786.11 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_F9F211DA3132

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Journal

Nature communications

Author(s)

Debackere K., Marcelis L., Demeyer S., Vanden Bempt M., Mentens N., Gielen O., Jacobs K., Broux M., Verhoef G., Michaux L., Graux C., Wlodarska I., Gaulard P., de Leval L., Tousseyn T., Cools J., Dierickx D.

ISSN

2041-1723 (Electronic)

ISSN-L

2041-1723

Publication state

Published

Issued date

17/06/2021

Peer-reviewed

Oui

Volume

Number

Pages

3705

Language

english

Notes

Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.

Keywords

Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Animals, Cell Line, Tumor, Cell Membrane/metabolism, Cohort Studies, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Forkhead Box Protein O1/genetics, Forkhead Box Protein O1/metabolism, Gene Expression Regulation, Neoplastic/genetics, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Kaplan-Meier Estimate, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism, Lymphoma, T-Cell, Peripheral/genetics, Lymphoma, T-Cell, Peripheral/metabolism, Lymphoma, T-Cell, Peripheral/pathology, Mice, Mice, Inbred C57BL, NF-kappa B/metabolism, Oncogene Proteins, Fusion/genetics, Oncogene Proteins, Fusion/metabolism, Proto-Oncogene Proteins c-fyn/genetics, Proto-Oncogene Proteins c-fyn/metabolism, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, RNA-Seq, Receptors, Antigen, T-Cell/metabolism, Signal Transduction/genetics, Sin3 Histone Deacetylase and Corepressor Complex/genetics, Sin3 Histone Deacetylase and Corepressor Complex/metabolism, bcl-X Protein/antagonists & inhibitors, bcl-X Protein/metabolism

URN

urn:nbn:ch:serval-BIB_F9F211DA31327

OAI-PMH

oai:serval.unil.ch:BIB_F9F211DA3132

DOI

10.1038/s41467-021-24037-4

Pubmed

34140493

Web of science

000665032700027

Open Access

Yes